Biomedical subjects

M H Chung

Publications and source records attributed to M H Chung.

At least 73 records · Page 4Linked to original sources

PubMed1997

Possibility of chemoprevention by the eradication of Helicobacter pylori: oxidative DNA damage and apoptosis in H. pylori infection.

OBJECTIVES: The purpose of this study was to study the changes of 8-hydroxydeoxyguanosine (8-OH-dG) contents of DNA from human gastric mucosa with or without Helicobacter pylori and the changes of two biomarkers, iNOS and apoptosis, in gastric biopsies obtained before and after the eradication of H. pylori. METHODS: DNA isolated from the biopsied human gastric mucosa was digested to deoxynucleotides by nuclease P1, then with Escherichia coli alkaline phosphatase, and analyzed by HPLC-ECD system. 8-OH-dG content was expressed as the number of residues per 10(5) deoxyguanosine. iNOS immunohistochemical staining was performed with antihuman iNOS antiserum generated in mice at a dilution of 1:500, and in situ apoptosis was detected by in situ terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling. Both the density of H. pylori and the degree of inflammation were scored. RESULTS: The 8-OH-dG contents of healthy normal controls with negative H. pylori were 4.31 +/- 2.33 (8-OH-dG/10(5) dG), whereas those of patients with positive H. pylori were 10.40 +/- 7.25. The difference between these two values was statistically significant (p < 0.01). The 8-OH-dG contents were significantly decreased after the eradication of H. pylori (12.22 +/- 2.09 vs. 2.42 +/- 1.22, p < 0.001). After the eradication of H. pylori, both the apoptotic index and the iNOS scores were significantly decreased, compared with those before eradication (3.72 +/- 1.74 vs. 1.17 +/- 1.06 for apoptosis and 10.34 +/- 6.79 vs. 1.43 +/- 1.14 for iNOS, p < 0.001). Statistically significant correlations were observed among apoptotic index, iNOS score, degree of inflammation, and density of H. pylori (p < 0.05). CONCLUSIONS: The increased levels of oxidative DNA damage, increased occurrences of apoptosis, and increased expressions of iNOS suggest mechanistic links between H. pylori infection and gastric carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1996

Induction of oh8Gua glycosylase in rat kidneys by potassium bromate (KBrO3), a renal oxidative carcinogen.

It has been suggested that 8-hydroxyguanine (oh8Gua), a DNA adduct formed by active oxygens, impairs the maintenance of genetic integrity, oh8Gua glycosylase removes oh8Gua residues as a free base from DNA strands. In E. coli, it has been demonstrated that oh8Gua glycosylase is induced in response to oxidative stress, but the oxidative inducibility in mammalian tissues has not yet been studied. In the present study, the inducibility of oh8Gua glycosylase was tested by comparing activity changes of this enzyme in the kidney and the liver of rats treated with potassium bromate (KBrO3). KBrO3 is known to cause oxidative damage to the kidney but not to other organs. With a single dose of KBrO3 (80 mg/kg, i.p.), activity in the kidney was found to increase significantly at 3 h compared to that at zero time. At 6 h, activity peaked, showing a 6-fold increase over that at zero time. Thereafter, it decreased and returned to its zero time level at 12 h. With increasing doses of KBrO3 (up to 160 mg/kg, i.p.), activity increased linearly with increased dosage, and over 40 mg/kg, i.p., activity increased to a level significantly higher than that in the control. In contrast to the time- and dose-dependent changes in activity in the kidney, no significant change was observed in the liver under the same conditions as above. These results show that oh8Gua glycosylase is also induced oxidatively in mammalian tissues. The induction in this tissue as well as in E. coli indicates that the adaptive response of this enzyme to oxidative stress is a general phenomenon in aerobic organisms and implies that the repair of oh8Gua residues in DNA is a process important for the survival of organisms in an aerobic environment.

Animals↗

PubMed1996

Induction of E. coli oh8Gua endonuclease by oxidative stress: its significance in aerobic life.

The induction of 8-hydroxyguanine (oh8Gua) endonuclease, a DNA repair enzyme for an oxidatively modified guanine, oh8Gua was studied in various growth conditions in Escherichia coli (AB1157). Anaerobically grown E. coli were found to have a very low activity of this enzyme while aerobically grown cells showed activity about 20 times that of the anaerobic level. Under the same condition, superoxide dismutase (SOD) showed about 6-fold increase in activity. A shift in growth conditions from anaerobic to aerobic resulted in rapid induction of this enzyme, and this induction was blocked (but not completely) by chloramphenicol. It is indicated that molecular oxygen is an effective stimulator to the induction of this enzyme and its induction depends partly on protein synthesis. Superoxide-producing compounds such as paraquat and menadione also increased the activity of endonuclease as well as SOD, but H2O2 showed no effect. Thus, superoxides are also implied as a stimulator. In contrast, hyperoxia induced only SOD not the endonuclease. This induction of the endonuclease by hyperoxia was only observed in a SOD-deficient strain (QC774). The aerobic activity of the endonuclease in QC774 was the same as that of wild types (AB1157, GC4468). It is implied that the responsiveness of oh8Gua endonuclease to superoxides is less sensitive than that of SOD. The endonuclease was also induced by a temperature shift from 30 to 43 degrees C and treatment with nalidixic acid. Among the stimuli used, molecular oxygen seems to be most effective for its induction. The inducible nature of this enzyme will serve as an important mechanism for the protection of oxidative DNA damage in the aerobic environment.

Aerobiosis↗

PubMed1996

Increased oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa.

Helicobacter pylori causes type B gastritis. It shows strong association with the development of gastric carcinoma. A plausible hypothesis for the missing link between H. pylori infection and gastric carcinogenesis involves oxygen free radical-induced DNA damage. To test this hypothesis, we compared the amount of 9-hydroxydeoxyguanosine, a marker for oxygen free radical-induced DNA damage, in the DNA of human gastric mucosa with and without H. pylori infection. Gastric antral biopsies were taken from pediatric patients and volunteers to select H. pylori-positive and H. pylori-negative specimens. The 8-hydroxydeoxyguanosine content of the gastric mucosal DNA was measured after H. pylori-positive and H. pylori-negative volunteers were identified. The increased level of oxidative DNA damage suggests the mechanistic link between H. pylori infection and gastric carcinoma.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1996

Increased 8-hydroxyguanine levels in DNA and its repair activity in rat kidney after administration of a renal carcinogen, ferric nitrilotriacetate.

The renal carcinogen, ferric nitrilotriacetate (Fe-NTA), is known to induce oxidative stress and the subsequent formation of a type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), in the rat kidney (Umemura et al., 1990). Using an improved DNA isolation method (Nakae et al., 1995), which reduces the background level of 8-OH-Gua, we found a five-fold increase in the 8-OH-Gua level in kidney DNA after a single i.p. injection of Fe-NTA. On the basis of the report that 8-OH-Gua repair activity is enhanced after cells are exposed to oxidative stress due to ionizing radiation (Bases et al., 1992), the measurement of 8-OH-Gua repair activity will also be useful to assess cellular oxidative stress. The 8-OH-Gua repair enzyme activity was determined with an endonuclease assay using a 22 mer DNA that contains 8-OH-Gua at a specific position. A five-fold increase in the 8-OH-Gua repair activity as compared with the control, was observed in the target organ, the rat kidney, 120 h after Fe-NTA administration. In the non-target organ, the liver, the increase was not as large (two-fold). This simple assay of oxidative DNA damage repair will be useful for evaluating the carcinogenicity of oxygen radical forming chemicals, in addition to chemical analyses of oxidative DNA damage.

Animals↗

PubMed1996

Oxidative status in senescence-accelerated mice.

The lipid peroxidation and activities of antioxidant enzymes were examined in the livers of two substrains of senescence-accelerated mice (SAM): senescence-resistant SAM-R/1 and senescence-prone SAM-P/1. Fluorescent age pigment and conjugated diene levels in both substrains increased gradually with age, but we found higher levels in SAM-P/1 at all ages tested. Differences in the levels of lipid peroxidation products became more marked with age. Among the enzymes studied, only mitochondrial superoxide dismutase (SOD) in SAM-P/1 showed decreased activity in all age groups. The specific mitochondrial SOD in that case was Cu,Zn-SOD. The amount of Cu,Zn-SOD in mitochondrial fractions of SAM-P/1 was only half that of SAM-R/1, whereas there were no apparent differences in the mRNA levels of both SAM groups. Our study indicates that impaired transport of Cu,Zn-SOD into mitochondria after cytosolic synthesis reduces defense against oxidative stress. That reduction may be one of the factors contributing to accelerated senescence in the SAM-P/1.

Aging↗

PubMed1996

Atypical polypoid adenomyofibromas (atypical polypoid adenomyomas) of the uterus. A clinicopathologic study of 55 cases.

We present the clinicopathological and immunohistochemical features of 55 atypical polypoid adenomyofibromas, a definitional expansion of an entity previously reported as "atypical polypoid adenomyoma" (APA) of the uterus. Patients ranged in age from 25 to 73 (mean, 39.9) years. All but two of the patients were premenopausal, and 14 were undergoing evaluation for infertility. Histologically, the lesions featured a biphasic proliferation of architecturally complex and cytologically atypical endometrial glands within a myofibromatous stroma. The histologic pattern ranged from widely separated and loosely clustered irregular but branched glands embedded in broad zones of cellular myofibromatous stroma to those possessing crowded, markedly complex, branching glands separated by sparse intersecting fascicles of fibromuscular tissue. The stroma in all cases was actin or desmin positive or both. Morular/squamous metaplasia was present in all but two cases and florid in most. All cases exhibited architecturally complex glands, and in 25 cases the architectural complexity was indistinguishable from that of well-differentiated endometrial adenocarcinoma, as we have defined it; that is, they had a high architectural index. Twenty-nine patients were initially treated with polypectomy or curettage followed by hormonal therapy; persistent or recurrent APA developed in 45% of the patients in this group (33% with low architectural index vs. 60% with high architectural index). Five patients had successful pregnancies despite persistent disease. Superficial myoinvasion was identified in the hysterectomy specimen in two of 12 APAs with a high architectural index but not in 21 APAs with a low architectural index. All patients are alive and well 1 to 112 months after diagnosis (mean, 25.2 months). On the basis of this study, we propose that APAs with markedly complex glands (high architectural index) be designated "atypical polypoid adenomyofibromas of low malignant potential" (APA-LMP) to emphasize the potential risk for myometrial invasion. A treatment program featuring local excision accompanied by close follow-up is warranted for APA despite the presence of recurrent or persistent disease. Patients with APA-LMP may also, in selected cases, be managed with less than hysterectomy, although (as with the usual well-differentiated carcinoma) there is a small but definite risk associated with this approach.

Adenomyoma↗

PubMed1996

Atypical polypoid adenomyofibroma (APA) versus well-differentiated endometrial carcinoma with prominent stromal matrix: an immunohistochemical study.

It can be extremely difficult in some cases to distinguish atypical polypoid adenomyomas (APAs) from invasive adenocarcinoma in an endometrial curettage or biopsy specimen. In order to determine if immunophenotypic features can be exploited to differentiate between these two entities in problematic cases, a series of APAs and myoinvasive well-differentiated endometrial carcinomas (WDCAs) were studied with a panel of standard immunohistochemical markers. All 23 APAs had stromal smooth muscle actin (SMA) reactivity, 12 of 23 had variable degrees of stromal desmin reactivity, and nine of 22 had CD34-positive stromal cells. All epithelial components of the APAs were cytokeratin (AE1 and CAM5.2) positive, whereas 22 of 23 were positive for estrogen receptor (ER) and progesterone receptor (PR). Among the 10 myoinvasive WDCAs, all contained at least some SMA-positive stromal cells, seven of 10 desmin-positive stromal cells, and four of eight CD34-positive stromal cells. All carcinomas studied demonstrated CAM5.2 and PR-positive epithelia; nine of 10 were ER positive. We conclude that the immunophenotype of APAs does not differ significantly from well-differentiated endometrial adenocarcinoma and that immunophenotyping is of little value in distinguishing APA from carcinoma. Because the stroma in APAs histologically and immunophenotypically more closely resembles a hybrid myofibromatous stroma, we prefer to refer to these lesions with the modified designation "atypical polypoid adenomyofibroma," although "APA" may be retained for clinical use.

Adenocarcinoma↗

PubMed1996

Acute eosinophilic pneumonia: radiographic and CT findings in six patients.

OBJECTIVE: Our objective was to assess the radiographic and CT findings of acute eosinophilic pneumonia. CONCLUSION: Initial and follow-up chest radiographs, chest CT scans (n = 5) and clinical data in six patients with acute eosinophilic pneumonia were reviewed by two chest radiologists. The predominant initial radiographic finding was diffuse bilateral reticular densities (four [67%] of six patients). Areas of ground-glass opacity were observed on CT scans in all patients (5 of 5) and were bilateral, random, and patchy in distribution in four (80%) of five patients. Smooth septal thickening and pleural effusions were observed in four patients. The disease manifested as rapid onset of severe dyspnea and fever and rapid resolution with (n = 3) or without (n = 3) steroid therapy. Bilateral reticular densities on chest radiographs and, on CT scans, ground-glass opacity with smooth septal thickening and pleural effusion associated with acute fever and dyspnea may suggest the diagnosis of acute eosinophilic pneumonia.

Acute Disease↗

PubMed1996

Establishment of primary cell culture from stria vascularis explants. Morphological and functional characterization.

To provide the prerequisite for long-term study of the inner ear related to structural and functional integrity, tissue of stria vascularis with spiral ligament was isolated from Wistar rat cochleas and cultured using the explant-culture technique. The following culture media were used: EMEM with Hepes buffer, hydrocortisone (400 ng/ml), transferrin (5 micrograms/ml). triiodothyronine (10(-9) M), cholera toxin (10(-10) M), insulin (5 micrograms/ml), and epidermal growth factor (10 ng/ml). To characterize the cells growing out from the explant, immunofluorescence with cytokeratin (cytokeratin 18) and ultrastructural examination with SEM and TEM were performed. The marginal cell function was investigated by expression of Na+, K(+)-ATPase antisera against beta 2 subunit of rat Na+, K(+)-ATPase and P-NPPase. We were able to maintain the cultured cells for 3 weeks or more. Monolayered marginal cells were observed beyond 14 days in vitro and the expression of cytokeratin 18 was especially enhanced. The cultured marginal cells were almost identical to in vivo cells both as regards ultrastructural features and Na+, K(+)-ATPase activity. The present results suggest that the primary explant culture technique is a reliable in vitro model of strial marginal cells. However, establishment of the cell line is needed for long-term study.

Animals↗

PubMed1996

Transmission of scrub typhus by needlestick from a patient receiving pefloxacin.

A nurse experience a needlestick during the care of a patient with scrub typhus, treated with pefloxacin (400 mg twice daily) and cefazolin. Seven days after the needlestick, pain and erythematous swelling developed at the tip of her left fourth finger, the site of the needlestick. Fever and headache developed 10 days later, and her skin lesion became a small vesicle surrounded by a dark erythematous area. The diagnosis of scrub typhus was made by a rising indirect immunofluorescent antibody titre, and her illness was improved with doxycycline.

Adult↗

PubMed1996

Pefloxacin-induced arthropathy in an adolescent with brain abscess.

We present a case of pefloxacin-induced arthropathy in a 15-year-old patient with brain abscess. Six joints were involved, of which the right elbow joint was most severely affected. Magnetic resonance imaging of the right elbow revealed joint effusion, and bone scintigraphy showed increased tracer uptake which was still present in the follow-up bone scans.

Adolescent↗

PubMed1996

Pathogenesis and prevention of stomach cancer.

In many Western developed countries, the incidence of stomach cancer has declined dramatically. This decrease was an extraordinary, "unplanned triumph", especially when compared to other cancers. Stomach cancer is still the most prevalent malignant tumor in Korea. Most Koreans carry Helicobacter pylori in their stomach. Thus, a new hypothesis, based on the relationship between the host and Helicobacter pylori, is presented as the carcinogenesis of human stomach cancer. The reasons for why the N-nitrosamide hypothesis should be dismissed as the etiology of stomach cancer, and why the contemporarily available principles and practice of intervention strategies to rapidly decrease the surprisingly high prevalence rate of Helicobacter pylori infection are impractical at this moment, are explained. In order to introduce an alternative provisional strategy of the "planned triumph" for the population vulnerable to stomach cancer, vitamin C is defined as an anti-inflammatory agent on the basis of the pathogenesis of Helicobacter pylori infection.

Animals↗

PubMed1996

Corpora amylacea: a marker for mesial temporal sclerosis.

Mesial temporal sclerosis (MTS) is the most frequently encountered abnormality in temporal lobectomies performed for medically intractable seizure disorders. The pathologic diagnosis of MTS relies on the identification of neuronal loss affecting various regions of the hippocampus. However, neuronal loss is often difficult to assess, particularly in lobectomies that are not performed en bloc. Because of this difficulty the presence of hippocampal pathology is often indeterminate. In this report we describe our experience with 73 temporal lobectomies performed for seizure disorders. In 58%, increased numbers of corpora amylacea (CoA) were found in association with MTS. The relationship between CoA and the pathogenetic mechanisms underlying MTS remains speculative. However, the association between MTS and corpora amylacea is important to recognize since the identification of abundant numbers of CoA provides a marker for MTS that can be useful in cases in which neuronal loss and gliosis are difficult to assess. For this purpose, it is strongly recommended that tissues resected from the hippocampus and amygdala for temporal lobe epilepsy be stained with LFB-PAS to highlight CoA.

Adolescent↗

PubMed1995

Intracerebral involvement in scleroderma en coup de sabre: report of a case with neuropathologic findings.

Linear scleroderma en coup de sabre (LScs) is a rare disorder not infrequently associated with neurologic symptoms, notably epilepsy. However, histopathologic documentation of intracerebral lesions in LScs is very limited and the etiology of the central nervous system symptoms has therefore never been convincingly established. We describe a 27-year-old woman with LScs and a longstanding history of epilepsy. Radiographic studies demonstrated a focal, intraparenchymal lesion in the left frontal lobe directly subjacent to the area of scleroderma on the forehead and scalp. The resected cerebral lesion revealed localized band-like sclerosis of the leptomeninges and associated vessels, as well as intraparenchymal calcifications and anomalous, ectatic vessels. These findings suggest that LScs may represent a neurocutaneous syndrome of vascular dysplasia similar to the Sturge-Weber syndrome, rather than a localized form of collagen vascular disease, as suggested by some.

Adult↗

PubMed1995

Effects of rebamipide on gastric cell damage by Helicobacter pylori-stimulated human neutrophils.

Helicobacter pylori stimulated human neutrophils to produce oxygen radicals as evidenced by the production of chemiluminescence in the presence of luminol. The capacity of H. pylori to produce oxygen radicals from neutrophils was much higher than that of Escherichia coli and Staphylococcus aureus and is almost as strong as that of PMA. Rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl] propionic acid) suppressed the chemiluminescence produced by H. pylori-stimulated neutrophils and also suppressed the chemiluminescence produced by a cell-free xanthine/xanthine oxidase reaction with luminol. Thus, it is indicated that this drug has the action of scavenging oxygen radicals. Gastric mucosal cells labelled with a fluorescent dye were damaged by the incubation of the cells with neutrophils and H. pylori, and this damage was protected by rebamipide. The protection of cell damage was ascertained as a decrease in the release of fluorescent dye into the incubation medium and a reduction in the distortion of cell geometry. The data suggest that H. pylori induce human neutrophils to produce oxygen radicals which are responsible for gastric mucosal cell damage and that rebamipide removes the oxygen radicals produced from H. pylori-activated neutrophils and thus reduces the gastric mucosal cell damage. These effects may account for the ulcerogenesis action of H. pylori and for part of the mechanism of the anti-ulcer action of rebamipide.

Alanine↗

PubMed1995

Proposed criteria for the diagnosis of well-differentiated endometrial carcinoma. A diagnostic test for myoinvasion.

Existing criteria for separating clinically benign but architecturally complex or cytologically atypical endometrial proliferations (hyperplasia or metaplasia) from well-differentiated endometrial carcinoma are underspecified and poorly reproducible, in part due to the absence of a uniformly agreed on methodologically independent outcome against which to judge the efficacy of competing sets of criteria. Because myoinvasion is the first unambiguous indicator of clinically aggressive behavior for proliferations in this spectrum, we have employed the presence or absence of myoinvasion as a tool to develop clinically meaningful diagnostic criteria for the separation of complex atypical hyperplasia/metaplasia from well-differentiated carcinoma (CAHM/WDCA). We obtained the paired endometrial samplings and hysterectomy specimens of 520 patients; these were split into a training set of 306 cases and a test set of 214. The presence or absence of myoinvasion was assessed from an examination of the hysterectomy specimen. For the purposes of this study, myoinvasion was defined as the presence of irregular intramyometrial glands surrounded by a granulation tissue-like response. To determine the morphologic features that were most predictive of myoinvasion, a series of endometrial architectural, cytological, and stromal features was initially evaluated on the training set (149 myoinvasive and 157 nonmyoinvasive). Using a variety of exploratory data techniques including the classification algorithm CART, we developed a diagnostic rule for predicting myoinvasion that employed one architectural feature (glandular complexity captured by a pictorial architectural index) and two cytological features (nuclear pleomorphism and prominence of nucleoli). Extensive squamous differentiation, fibroblastic stroma, necrosis, stromal foam cells, and other cytologic features did not provide additional predictive value when cross-validated. The true misclassification rate of the CART-generated prediction rule was further assessed by applying the rule to the test set drawn largely from community hospitals. The sensitivity and specificity of this rule for detecting myoinvasion was 99.5 and 57%. The likelihood ratio was 2:1, (i.e., using prior odds of myoinvasion in the CAHM/WDCA spectrum of 1:10, the posterior odds on myoinvasion using the CART-generated rule would be 1:5). Comparison of the CART-generated myoinvasion prediction rule with the Kurman and Norris endometrial stromal invasion criteria for well differentiated endometrial carcinoma (25), using receiver operator characteristic curve (ROC) techniques, demonstrated a significant improvement in the ability to separate myoinvasive from non-myoinvasive endometrial proliferations with the CART-generated rule; the average area under the curve for the CART-generated rule was 0.78 (SE = 0.02) versus 0.67 (SE = 0.03) for the endometrial stromal invasion criteria.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

PubMed1995

Lipid peroxidation and 8-hydroxydeoxyguanosine formation in rats fed fish oil with different levels of vitamin E.

This study was conducted to investigate the protective role of vitamin E against the formations of lipid peroxides in plasma and tissues and of 8-hydroxydeoxyguanosine (8-OHdG) in livers of rats fed fish oil. Six-week-old male Sprague-Dawley rats were divided into four groups and fed experimental diets for 8 weeks. Three fish oil (F) groups were fed a menhaden fish oil and soybean oil (9:1) mixture as 10% (wt/wt) of their diet. These three groups (F0, FI, and FII) were provided with < or = 3, 45, and 209 IU of vitamin E/kg diet, respectively. The SI group was fed soybean oil with < or = 45 IU of vitamin E/kg diet. The F0 group had the highest levels of thiobarbituric acid-reactive substances (TBARS) in plasma (per milligram lipid), and liver, lung, heart, and kidney. The FI group had higher levels of TBARS than the SI group in plasma and tissues except the lung. In liver, the TBARS levels of the FII group were also higher than those of SI group, but in other tissues, similar levels were observed in the FII and SI groups. Plasma level of vitamin E was lowest in F0 group and vitamin E levels were generally lower in F groups than in SI group. These levels were expressed as vitamin E per milliliter of plasma. However, plasma E levels were similar when expressed per milligram plasma lipid. The liver 8-OHdG concentration tended to decrease as dietary vitamin E increased in the F groups, but there was no difference in the level of 8-OHdG between the FI and SI groups. These results suggest that vitamin E should be supplemented in fish oil feeding to prevent the enhanced lipid peroxidation and the formation of 8-OHdG in the body.

Administration, Oral↗